In recent years, microRNAs (miRs, miRNAs) have emerged as an important novel class of regulatory RNA, which have a profound impact on a wide array of biological processes. These small (typically 17-24 nucleotides long) non-coding RNA molecules can modulate protein expression patterns by promoting RNA degradation, inhibiting mRNA translation, and also affecting gene transcription. miRs play pivotal roles in diverse processes such as development and differentiation, control of cell proliferation, stress response and metabolism. The expression of many miRs was found to be altered in numerous types of human cancer, and in some cases strong evidence has been put forward in support of the conjecture that such alterations may play a causative role in tumor progression. There are currently about 875 known human miRs.
Gastric cancer is a highly aggressive and lethal malignancy. On a global basis, this tumor represents 8.6% of the entire cancer burden and the second leading cancer cause of death; in the year 2002, over 930,000 new cases of gastric cancer were expected and nearly 700,000 people were expected to die from the disease. Surgical resection is the standard treatment of localized gastric cancer. Its results however are generally disappointing; approximately 70% of patients undergoing successful complete (R0) resection will still experience recurrence. Attempts to improve patients outcome following surgery by using adjuvant therapy have only lead to modest improvement: trials using either postoperative chemoradiation or perioperative chemotherapy have demonstrated an absolute 10-15% reduction of the risk of recurrence. Moreover, adjuvant therapy, as given in these trials, was associated with significant morbidity and even mortality.
The unsatisfying results of surgery and the limited benefit from adjuvant therapy and its toxicity, all emphasize the need for an improved selection of patients for the various treatment strategies. For example, patients with good prognosis may be spared adjuvant therapy whereas those with poor prognosis may receive such treatment or may even be offered investigational programs. However, the current ability to determine the prognosis of an individual patient is limited and is mainly based on the extent of the local tumor spread, i.e. the TNM staging. Other prognostic factors, such as the tumor's grade, vascular invasion and perineural spread, add only little to the ability to distinguish between patients with good and bad prognosis.
The determination of the gastric cancer characteristics has a potential prognostic value and can be used to design an optimal therapy. Thus characterization of the molecular biological properties of a particular tumor could lead to a more specific and efficient therapy. A therapy could be tailored according to the molecular features of the tumor to decrease the risk of recurrence of the disease.
Furthermore monitoring means a close follow up of the disease after initial therapy. Classical clinical methods are quite insensitive for the detection of the recurrence of tumors, so that the disease will reach a progressed stage before it is found. This fact reinforces the need for a more accurate prognostication method, as close monitoring cannot lead to cure of patients who did not receive the optimal primary treatment and have recurred.
There is a variety of tools to assess the primary diagnosis in tumors such as gastric tumors. Yet, due to the diversity of the molecular characteristics of tumors, the outcome of detected tumors may vary widely. For assessing prognosis and tailoring an adequate therapy further characterization of the tumors is indispensable. In many tumors prediction of the course and the treatment necessary can be assisted by testing for the level of expression of several tumor markers. Based upon this prognosis it may be possible to choose a treatment for the particular tumor to ensure the best chances for the patient along with the lowest necessary therapeutic burden. For gastric cancer the classical methods of staging and grading of the tumor afford only a restricted prognosis, so that potentially harmful therapies are applied to avoid recurrence of tumors. If the aggressiveness of tumors could be diagnosed on the basis of molecular markers, the therapy could be better suited to the needs of the individual case.
Thus, there exists a need for identification of biomarkers that can be used as prognostic indicators for gastric cancer.